Negative View of Birth Experience Found to Be Associated With Elevated Postpartum Anxiety

A more negative perception of a recent childbirth experience is associated with elevated symptoms of postpartum anxiety, but not postpartum depression, according to a study in the April issue of the Archives of Women’s Mental Health.

The findings suggest that improving the childbirth experience for women may help to reduce postpartum anxiety, which is believed to affect some 13 to 19 percent of women during the first year following childbirth. Past studies show that postpartum depression and anxiety can compromise mother-infant interactions and child development.

To determine whether childbirth factors such as mode of birth, interventions, complications, and women’s experience are associated with elevated symptoms of depression and anxiety, researchers from the United States and United Kingdom examined the medical records from a sample of nearly 5,000 women living in the United Kingdom who gave birth between April 1991 and December 1992 and participated in the Avon Longitudinal Study of Parents and Children. The Edinburgh Postnatal Depression Scale was used to assess elevated symptoms of depression (score of greater than or equal to 13) and the Crown-Crisp Experiential Index was used to assess elevated symptoms of anxiety (score greater than or equal to 9) at two and eight months after delivery. The researchers compared women who described the recent birth experience as “wonderful” with those who described it as “not wonderful/not sure.”

A more negative perception of the birth experience was associated with elevated symptoms of anxiety at two months (odds ratio [OR]=1.52) and eight months (OR=1.30) postpartum but was not associated with elevated symptoms of depression at either time point. Type of delivery (physiological [defined as no drug exposure except nitrous oxide] versus non-physiological [interventions of pain medication, oxytocin, cesarean]) and immediate postpartum complications were not associated with elevated symptoms of depression or anxiety.

“Reducing postpartum anxiety will likely improve mother-infant interaction and infant development and may even reduce the incidence of posttraumatic stress related to childbirth,” the authors wrote. “Given the known psychosocial risk factors of postpartum depression; the emerging research on hormonal, genetic, and epigenetic biomarkers of depression; and the frequent comorbidity of postpartum depression and anxiety, future research is warranted to identify psychosocial and biological risk factors unique to postpartum anxiety.”

For related information, see the Psychiatric News article “Early Postpartum Depression Screenings Not Enough to Identify High-Risk Women.”

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Study Suggests SSRIs Do Not Increase Risk of Adverse Cardiovascular Outcomes

People with depression are more likely to develop cardiovascular disease and have a higher mortality rate than the general population, but whether antidepressants alter this risk remains unknown. A study published in the BMJ now suggests selective serotonin reuptake inhibitors (SSRIs) are not associated with an increased risk of adverse cardiovascular outcomes such as heart attack and stroke and may even decrease the risk of these events.

Researchers from the United Kingdom led a retrospective study of nearly 240,000 patients aged 20 to 64 who were first diagnosed with depression between January 2000 and July 2011. The authors tracked antidepressant prescriptions and diagnoses of myocardial infarction, stroke/transient ischemic attack, and arrhythmia during a five-year period following the initial depression diagnosis.

During the follow-up period, 209,476 (87.7%) patients received a total of 3,337,336 antidepressant prescriptions (71.3% of these prescriptions were for SSRIs), and there were 1,452 new diagnoses of arrhythmia, 772 new diagnoses of myocardial infarction, and 1,106 new diagnoses of stroke or transient ischemic attack.

The researchers found no evidence that SSRIs are associated with an increased risk of arrhythmia, myocardial infarction, or stroke/transient ischemic attack, but there was some indication that the medications are associated with a reduced risk of myocardial infarction and arrhythmia. Citalopram—an SSRI that has been found to cause dose-dependent QT interval prolongation—was not associated with arrhythmia, even at high doses (greater than or equal to 40 mg/day). In contrast, the risk of arrhythmia was increased during the first 28 days of taking tricyclic and related antidepressants.

“Prescription of antidepressants is a complex process, involving balancing of risks and benefits for different antidepressants and doses, accounting for severity of depression, and considering patients’ risk factors, comorbidities, and preferences,” the authors wrote. “These findings are reassuring in light of recent safety concerns about selective serotonin reuptake inhibitors.”

For related information, see the Psychiatric News article “Antidepressants May Help Improve Heart Health.”

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White House Announces Proposal to Raise Cap on Buprenorphine Prescribing

Today, President Obama is announcing a host of public and private sector initiatives addressing the nation’s opioid epidemic, including a proposal to increase the current patient limit for qualified physicians who prescribe buprenorphine to treat opioid use disorders from 100 to 200 patients.

Additionally, more than 60 medical schools are announcing that, beginning in fall 2016, they will require their students to take some form of prescriber education, in line with the newly released Centers for Disease Control and Prevention Guideline for Prescribing Opioids for Chronic Pain, to graduate.

The proposals met with preliminary approval from APA leaders. “These are very important steps to improve the accessibility of buprenorphine,” Frances Levin, M.D. (pictured above), chair of the APA Council on Addiction Psychiatry, told Psychiatric News. “The problem, however, is getting physicians more comfortable prescribing [buprenorphine], since there are already many physicians who are certified but don’t prescribe or underprescribe.

“Training physicians while they are residents is a very good strategy,” she said. “We need a grassroots approach.”

Her comments were echoed by John Renner, M.D., vice chair of the council. “Our survey of addiction clinicians indicates that the majority are not comfortable treating numbers of patients in [the 150-200 patient] range,” he told Psychiatric News. “It is possible that this change will create a number of large buprenorphine practices, but it will not generate the numbers needed to impact the current epidemic. We remain committed to our proposal to expand treatment services by also encouraging a larger number of small buprenorphine practices by expanding clinician training, permitting prescribing by physician assistants and nurse practitioners, and addressing clinicians’ concerns about the system of DEA inspections.”

The president’s remarks were made at the National Rx Drug and Heroin Abuse Summit in Atlanta. Also speaking at the summit was psychiatrist Patrice Harris, M.D., who is chair of the American Medical Association's Task Force to Reduce Opioid Abuse. As part of her remarks, she encouraged physicians to use state Prescription Drug Monitoring Programs.

“We urge physicians to register and use the state prescription drug monitoring program to check a patient's prescription history; educate yourself on managing pain and promoting safe, responsible opioid prescribing; support overdose prevention measures, such as increased access to naloxone; reduce the stigma of substance use disorders and enhance access to treatment; and ensure patients in pain aren't stigmatized and can receive comprehensive treatment.”

For more information, see the Psychiatric News article “Why Aren’t More Physicians Prescribing Buprenorphine?”

APA Applauds Ga. Governor's Decision to Veto Controversial 'Religious Freedom' Bill

Georgia Gov. Nathan Deal (left) announced earlier today that he will veto House Bill 757, a controversial "religious freedom" bill that APA criticized for permitting sexual- and gender identity-based discrimination.

“The American Psychiatric Association applauds Gov. Nathan Deal’s pledge to veto HB 757, which would have opened the door to state-sanctioned discrimination of LGBTQ people,” said APA CEO and Medical Director Saul Levin, M.D., M.P.A., in a press statement. “APA spoke out against the bill, and we are glad that our voice was heard. Gov. Deal was correct when he said the bill does not fit into the character of the state, a welcoming state with friendly people.”

On March 23, APA President Renée Binder, M.D., and Levin sent a letter to Gov. Deal urging the veto, noting that all forms of discrimination, whether societal, religious, or family stigma, may adversely affect the mental health of individuals and necessitate intervention.

“APA has long opposed discrimination against individuals in the LGBTQ community, whether that discrimination occurs in accessing health care services, education, employment, government services, housing, military service, or spousal rights,” Binder and Levin wrote.

In addition to sending the letter, APA joined Georgia Prospers, a coalition of more than 500 businesses opposed to HB 757.

For related information on the mental health implications of discrimination against individuals from sexual or gender minority groups, see the Psychiatric Services article "Severe Mental Illness in LGBT Populations: A Scoping Review."

Stress in Pregnancy May Affect Genes for Neural Development

Greater perceived stress in pregnant women was associated with alterations of two genes in the placenta and also with an important measure of fetal neurodevelopment, according to a study published today in the American Journal of Psychiatry posted at AJP in Advance.

"[E]ven the relatively common life experiences of feeling unable to 'control important things in your life' and 'cope with all the things you have to do' are associated with alterations of DNA functioning in the placenta that, in turn, affect fetal development," wrote Catherine Monk, Ph.D., an associate professor of psychiatry, behavioral medicine, and developmental neuroscience at Columbia University Medical Center, and colleagues.

The women's distress was linked to increased methylation of the HSD11B2 and FKBP5 genes in the placenta and reflected in reductions in fetal coupling. "Coupling" is the correlation between fetal movement and heart rate that develops during gestation and which "is positively associated with more mature neural integration at birth," wrote Monk and colleagues.

Since a mother’s adverse pregnancy experiences are known to increase the child’s risk for psychopathology, the results "add molecular support" and "proximal evidence for the putative prenatal shaping of children’s mental health trajectories."

For more in Psychiatric News about the effects of stress in pregnancy, see "Researchers Tackle Complexity of Intergenerational Stress Transmission."

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Antioxidant May Help Patients Resist Urge to Pick Skin

Although excoriation (skin-picking) disorder is estimated to affect 1.4% to 5.4% of the population, there are limited data regarding the underlying pathophysiology and treatment of the behavior. A study published Wednesday in JAMA Psychiatry now suggests that acute treatment with N-acetylcysteine may decrease skin-picking behaviors in people with the disorder. N-acetylcysteine is a precursor to the antioxidant enzyme glutathione and acts on the cysteine-glutamate exchange mechanism.

Previous studies have suggested that glutamatergic dysfunction may play a role in the pathophysiology of compulsive and related disorders, and N-acetylcysteine—an amino acid known to increase extracellular levels of glutamate in the nucleus accumbens—may help to reduce these behaviors.

To test whether N-acetylcysteine was more effective than placebo in decreasing compulsive skin-picking behaviors, Jon Grant, J.D., M.D., M.P.H., a professor of psychiatry and behavioral neuroscience at the University of Chicago, and colleagues randomly assigned 66 adults aged 18 to 65 with a current DSM-5 diagnosis of excoriation disorder to 12 weeks of daily N-acetylcysteine (1,200 mg/day to 3,000 mg/day) or placebo treatment. Every three weeks, researchers evaluated the participants, using measures of skin-picking severity, including the modified Yale-Brown Obsessive Compulsive Scale (NE-YBOCS) and the Clinical Global Impression-Severity Scale.

Of the 66 participants in the trial, 59 were women, with a mean age of 34.8 years. At the end of 12 weeks, the NE-YBOCS total score demonstrated a 38.3% reduction in skin-picking symptoms for the N-acetylcysteine group (from 18.9 at baseline to 11.5 at 12 weeks) compared with 19.3% for placebo (from 17.9 at baseline to 14.1 at 12 weeks). The CGI-Improvement Scale score also demonstrated significant improvement by study end point: of the 32 participants who completed the study, 15 (47%) participants assigned to treatment with N-acetylcysteine were much or very much improved compared with 4 (19%) of the 21 in the placebo group who completed the study. However, treatment with N-acetylcysteine failed to produce statistically significant improvement in measures of psychosocial functioning or quality of life.

The authors offered several explanations as to why significant improvements in psychosocial or quality of life were not seen in the small trial, including the limitations of not assessing functional and quality-of-life improvements over a longer period of time. Another limitation was that the study did not include psychotherapy, which has been found to benefit patients with skin-picking disorder, they noted.

Nonetheless, the authors concluded, “This investigation suggests that N-acetylcysteine appears to be effective and well tolerated in the acute treatment of SPD [skin-picking disorder]. As effective treatments for skin picking emerge, it becomes increasingly important that physicians and other mental health care professionals screen for the disorder to provide timely treatment.”

For related information, see the Psychiatric News article “How to Recognize, Treat Body Dysmorphic Disorder.”

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FDA Announces Safety Labeling Changes for Immediate-Release Opioid Medications

The Food and Drug Administration (FDA) announced yesterday that it has issued class-wide safety labeling changes for immediate-release (IR) opioid pain medications in an ongoing effort to educate prescribers and patients about the potential risks associated with opioid use. Among the changes, the FDA is requiring a new boxed warning about the serious risks of misuse, abuse, addiction, overdose, and death from IR opioids, which are intended for use every four to six hours.

“IRs [opioids] are the most frequently prescribed type of opioid medication,” said Douglas Throckmorton, M.D., deputy director of regulatory programs at the FDA’s Center for Drug Evaluation and Research, during a conference call. Until now, very few IR opioids have received labeled warnings, he explained. (In 2013, the FDA required class-wide labeling changes for extended-release and long-acting [ER/LA] opioid analgesics—intended to be taken once or twice a day—which included modifications to the products’ indications, limitations of use, and warnings.)

As part of the boxed warning on IR opioids, the FDA will now require a precaution that chronic maternal use of opioids during pregnancy can result in neonatal opioid withdrawal syndrome in offspring, which may be life-threatening if not recognized and treated properly.

In addition, the FDA is requiring updated labeling for all opioids—both IR and ER/LA products—to include safety information about potentially harmful drug interactions with antidepressants and medicines intended to treat migraines that can result in a serious central nervous system condition called serotonin syndrome.

Modified labeling for all opioids will also include information about opioid effects on the endocrine system, including a rare but serious disorder of the adrenal glands (called adrenal insufficiency) as well as decreased sex hormone levels (androgen deficiency). The labeling changes will make it clear that these negative outcomes can occur whether a patient is taking an opioid to treat pain or if the product is being used for medication-assisted treatment for opioid use disorder.

The FDA is currently reviewing available scientific information about potentially serious outcomes related to interactions between benzodiazepines and opioids. Once this review is completed, the FDA will take necessary actions to ensure prescribers and the public are informed of the risks involved with the use of these medications.

To read more about recent FDA efforts to combat the prescription opioid epidemic, see the Psychiatric News article “FDA Officials Propose Strategy for Tackling Prescription Opioid Epidemic.”

(Image Courtesy of the Food and Drug Administration)

Appetite Early in Risperidone Treatment Found to Predict Metabolic Changes in Kids With ASD

Rapid weight gain in the first eight weeks of treatment appears to predict metabolic complications in children and adolescents taking risperidone for autism spectrum disorder (ASD), according to a report appearing online in the Journal of the American Academy of Child and Adolescent Psychiatry.

The results indicate that appetite, body weight, and waist circumference should be monitored early and regularly during treatment, the researchers stated.

Researchers from the National Institute of Mental Health (NIMH) and several other institutions monitored weight, waist circumference, body mass index, and metabolic changes in 124 children with ASD and serious behavioral problems, assigned to take risperidone for 24 weeks. 

Ninety-seven patients remained in the trial at 24 weeks (75 participants had a reported increase in appetite in the first eight weeks of treatment compared with 22 participants without such reports), with an average weight gain of 5.4 kg. Increased appetite early in treatment predicted weight gain and higher BMI scores over time.

Weight gain precipitated a “cascade” of metabolic effects: from pretreatment to week 16, there were significant increases in glucose, hemoglobin A1c, insulin, and other variables associated with metabolic syndrome. At baseline, seven patients had met conventional criteria for metabolic syndrome, but by week 16, 12 additional patients were so classified.

“The main practical finding of the study is that the metabolic adverse effects of this commonly used antipsychotic seem to begin with a drug-induced increase in appetite that occurs very early after starting treatment and leads to increased caloric intake and then rapid increase in weight, which is followed by elevation in blood sugar and lipids,” Bendetto Vitiello, M.D., chief of the Child and Adolescent Treatment and Preventative Intervention Research Branch at NIMH, told Psychiatric News. “So, the cascade of adverse metabolic events is precipitated by the increase in appetite and food intake. Proactive interventions aimed at controlling caloric intake at the very beginning of treatment may be able to prevent or attenuate the negative metabolic effects of the medication.”

For related information, see the Psychiatric News article “Exposure to Antipsychotics May Increase Risk of Type 2 Diabetes in Youth.”

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Using Omega-3 Fatty Acids as Add-On Therapy Might Benefit Patients With MDD

Many studies have looked into the role of omega-3 fatty acids in treating depression, either as an alternative therapy or an add-on to antidepressants, and the findings have been mixed; as such, several meta-analyses combining the available data have not found any definitive benefit to these nutritional supplements.

A meta-analysis published in Translational Psychiatry, however, suggests that omega-3 fatty acids can help improve the symptoms of major depressive disorder (MDD) in certain cases—notably in instances when patients have a confirmed MDD diagnosis and are taking antidepressants.

The analysis combined 13 placebo-controlled studies carried out between 2002 and 2015 that included 1,233 participants; in an effort to create a more discrete population sample, only studies with adult patients who had primary depression assessed using clinical interviews and DSM criteria for MDD were included. Studies of people with perinatal, perimenopausal, or MDD associated with another neuropsychiatric disorder were excluded.

After combining these studies, the authors found that omega-3 supplementation did result in a statistically significant improvement of depressive symptoms compared with placebo. (Most of the studies used the Hamilton Rating Scale for Depression to measure the changes.)

When looking at potential contributing factors, the authors found that studies using higher doses of eicosapentaenoic acid (EPA, with study doses ranging from 0-4400 mg/daily) or using omega-3s as add-ons to antidepressant therapy had stronger results. The levels of docosahexaenoic acid (DHA, 0-2200 mg/daily) had no bearing on outcomes, nor did the EPA/DHA ratio.

"This is a balanced analysis that has incorporated several recent studies that have been more rigorous in diagnosing the enrollees," said David Mischoulon, M.D., Ph.D., an associate professor of psychiatry at Massachusetts General Hospital and a co-author on two of the studies incorporated in this analysis.

"The findings are in agreement with other work suggesting that the anti-inflammatory properties of EPA might be a contributing factor. More work uncovering the mechanisms of how EPA and antidepressants might interact would be worthwhile," he continued.

To read more about how food intake and nutrition can be important in psychiatry, see the Psychiatric News article “Food May Be a Tool to Consider When Helping Psychiatric Patients.”

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Associations Between Psychotic Experiences, Mental Disorders Found to Be Bidirectional

While previous studies suggest that psychotic experiences are associated with an elevated risk of subsequent mental disorders, the findings of a study published online today in AJP in Advance also suggest that most mental disorders are associated with an elevated risk of subsequent psychotic experiences.

John McGrath, M.D., Ph.D. (pictured above), a professor of psychiatry at the University of Queensland in Brisbane, Australia, and colleagues drew on data gathered by trained lay interviewers on 31,261 people in 18 countries as part of the World Health Organization’s World Mental Health Surveys. They were looking not just for prevalence of psychotic experiences and mental illnesses but for any temporal associations between the two.

Of the 21 common mental disorders studied, psychotic experiences were significantly associated with subsequent first onset of eight disorders (major depressive disorder, bipolar disorder, generalized anxiety disorder, social phobia, posttraumatic stress disorder, adult separation anxiety disorder, bulimia nervosa, and alcohol abuse). In contrast, 18 of the 21 mental disorders were linked with subsequent first-onset psychotic experiences, with odds ratios ranging from 1.5 to 2.8 depending on the illness.

“These findings call into the question the specificity of the association between psychotic experiences and psychotic disorders,” the researchers wrote. “A better understanding of how psychotic experiences unfold across the lifespan and interact with mental disorders may provide clues to help guide clinical management.”

In a related video, McGrath describes the study in more detail and what the findings might mean for clinicians.

For related information, see the Psychiatric News article “Same Brain Circuits Linked With Psychosis in Two Disorders.”

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Help Make ECT Accessible to More Patients

The Food and Drug Administration (FDA) is proposing to reclassify ECT from a Class III (high risk) medical device to Class II (low risk), a change APA supports. APA urges psychiatrists to contribute their comments to the FDA in favor of the reclassification. A template letter has been prepared that provides talking points. The FDA must receive comments by March 28.

“[I]t is so important for psychiatrists to take the lead in expressing their views in regard to the role that ECT plays in clinical practice and in the treatment of major depressive disorder,” wrote APA CEO and Medical Director Saul Levin, M.D., M.P.A., and APA President Renée Binder, M.D., in a blog post. “For appropriate patients, ECT has been a lifesaver. It has given them an opportunity for a normal, functional life.”

For information about previous efforts to reclassify ECT, see the Psychiatric News article “FDA Advisory Panel Favors ECT in High-Risk Category.”

Depression Trajectories May Help Identify Older Adults at Greatest Risk of Dementia

Older adults who exhibit a pattern of chronically elevated and increasing depressive symptoms over time may be at higher risk of subsequently developing dementia, according to a study published yesterday in JAMA Psychiatry. The findings suggest that tracking depressive symptoms in older adults may help identify those at greatest risk of dementia.

Whether depression increases risk of dementia or is a symptom of cognitive decline remains an area of active investigation. While some findings have suggested that older adults develop depression in response to the experience of cognitive decline, others have pointed to depression as a risk factor for cognitive decline. Most of these studies, however, assessed the depressive symptoms of older adults at a single point in time, limiting the ability of researchers to capture symptom variability within individual patients or the longitudinal course of depression.

In the current study, Allison Kaup, Ph.D., an assistant professor of psychiatry at the University of California, San Francisco, and colleagues evaluated whether the depressive symptom trajectories of 2,488 older adults captured over a five-year period (1997-1998 through 2001-2002) were associated with the development of dementia at follow-up six years later (2007-2008). Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale Short Form at years 1, 3, 4, and 5 of the study. Incident dementia was determined based on hospital records, medication use, and decline in global cognitive functioning.

Overall, 353 participants (14.2%) developed dementia over the course of the follow-up period and did so a mean of 3.9 years after the depressive symptom assessment period. Compared with individuals with consistently minimal depressive symptoms, those with high and increasing symptoms were significantly more likely to develop dementia.

“Whether depression is a risk factor for dementia versus a symptom of an underlying neurodegenerative process is a complex question. Although our study cannot fully disentangle these possibilities, our results suggest the nature of the depression-dementia relationship may differ depending on the pattern of depressive symptoms,” the authors wrote. “Our results suggest that individuals’ trajectory of depressive symptoms may inform dementia risk above and beyond assessment of depressive symptoms at one time point alone.”

For related news, see the Psychiatric News article “Older Adults With Depression, Cognitive Impairment May Benefit From Psychosocial Therapy.”

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CDC Releases Guideline for Prescribing Opioids for Chronic Pain

The Centers for Disease Control and Prevention (CDC) has issued a guideline for clinicians who are prescribing opioids for chronic pain that is not associated with cancer, palliative care, or end-of-life care. The guideline is intended to ensure that clinicians and patients consider safer and more effective treatment options for pain management, improve patient outcomes, and reduce the number of people who develop opioid use disorder, overdose, or experience other adverse events related to these drugs.

“The new guideline really points out the dangers of the liberal prescribing of opioids,” said Petros Levounis, M.D, M.A., an addiction expert and chair of the Department of Psychiatry at Rutgers New Jersey Medical School. “Addiction psychiatry has been at the forefront of the fight against the opioid epidemic for at least 10 years now, from preventing the initiation of opioids to supporting the use of treatment for opioid addiction with FDA-approved medicines such as buprenorphine,” he told Psychiatric News.

The guideline includes 12 recommendations, which address when to initiate or continue opioids for chronic pain; opioid selection, dosage, duration, follow-up, and discontinuation; and assessing risk and addressing harms of opioid use: 

Nonpharmacologic (e.g., physical therapy, cognitive-behavioral therapy) and non-opioid therapies (e.g., NSAIDs, acetaminophen) are preferred for chronic pain. The CDC recommends that clinicians should consider opioid therapy only if expected benefits outweigh risks to the patient. If opioids are used, they should be combined with nonpharmacologic therapy and non-opioid pharmacologic therapy, as appropriate. 

When opioids are used, the lowest possible effective dosage should be prescribed to reduce risks of opioid use disorder and overdose. The CDC recommends that clinicians should evaluate benefits and harms with patients within one to four weeks of starting opioid therapy for chronic pain or of dose escalation. 

Health care professionals should always exercise caution when prescribing opioids and monitor all patients closely. Because mental illness can affect pain and function in patients with chronic pain, the CDC recommends that clinicians use validated instruments to assess for anxiety, posttraumatic stress disorder, and/or depression that might help clinicians improve treatment outcomes. 

Clinicians should offer or arrange evidence-based treatment (usually medication-assisted treatment with buprenorphine or methadone in combination with behavioral therapies) for patients with opioid use disorder. For patients with problematic opioid use that does not meet criteria for opioid use disorder, the CDC recommends clinicians should offer to taper and discontinue opioids.

“Although some of the items in the guideline are not supported by as much scientific evidence as we would like to appropriately make these recommendations [such as dosing], at least this is a good start in helping to address prescription practices concerning opioids,” Levounis added.

For related information on the FDA’s Opioid Action Plan, see the Psychiatric News article “Robert Califf, M.D., Confirmed as FDA Commissioner.”

(Image: Courtsey of CDC)

Despite Effectiveness, Buprenorphine Remains Underprescribed

Experts say buprenorphine is the ideal medication for opioid addiction—the partial agonist satisfies cravings without the same level of euphoria that drives drug-seeking behavior. Yet, the medication is underused and underprescribed, according to experts who spoke with Psychiatric News.

According to statistics from the Substance Abuse and Mental Health Services Administration (SAMHSA), there are just 31,862 physicians certified to prescribe buprenorphine—and 40 percent of these physicians do not prescribe buprenorphine at all.

A recent Psychiatric News article explored several factors that may deter physicians from prescribing the medication and create access challenges for patients. To address this access problem, APA supports incrementally expanding the number of patients that certified buprenorphine providers are permitted to treat at one time.

“I like to think of buprenorphine as a pharmacological platform that takes away withdrawal,” said John Renner, M.D., vice chair of the APA Council on Addiction Psychiatry and president of the American Academy of Addiction Psychiatry (pictured above). “It does not resolve whatever problems led an individual to seek out drugs in the first place, but what does change is that the patient’s life is not dominated by drug-seeking. The pharmacological platform makes recovery possible.”

While buprenorphine is a highly effective treatment for opioid addiction, experts agreed that it should be prescribed as part of a total addiction treatment plan including participation in 12-step recovery and/or psychotherapy.

For more about buprenorphine prescribing and APA training to receive the waiver necessary to prescribe, see the Psychiatric News article “Why Aren’t More Physicians Prescribing Buprenorphine?”

Psychoeducation Improves Compliance, Outcomes in Patients With Schizophrenia

Psychoeducation appears to improve long-term medication adherence in patients with schizophrenia, leading to significantly fewer days spent in a hospital, according to a study published in Schizophrenia Bulletin. Despite taking a higher average dose of chlorpromazine, the patients in the trial did not experience significant increases in motor side effects when assessed at a seven-year follow-up.

These findings are a component of a large randomized, controlled trial known as the Munich PIP (Psychosis Information Project) study, which found that patients who participated in a program where they learned about the nature of their illness and the importance of treatment over the course of several months were more likely to adhere to their chlorpromazine regimen seven years later compared with patients who received standard guidance. As part of the main study analysis, the researchers found that the patients who received psychoeducation took more medication over time and had a lower rehospitalization rate at two-year and seven-year follow-ups.

In the current study, a group at the Technical University of Munich explored the potential of increased movement problems in a subset of 41 patients taking chlorpromazine (21 receiving psychoeducation and 20 controls) using both the standard rating scale (Abnormal Involuntary Movement Scale or AIMS) and a detailed series of kinematic tests (e.g., repetitive drawing and hand steadiness).

Despite taking a higher average daily dose of chlorpromazine (354 units versus 279 units), the patients in the psychoeducation group did not show any significant deficiencies in their assessed movement skills at the seven-year follow-up. Additionally, the researchers found patients in the intervention group had spent 74.7 days in a hospital compared with 243.4 days for the patients in the control group—about the same rates as the larger Munich PIP cohort.

“Psychoeducation can lead to a significant improvement of long-term outcome and save treatment costs, above all, by the reduced number of hospital days. Being better informed and thus better empowered, patients can positively influence their medical treatment and reduce side effects in the long run,” the authors wrote.

To read more about the potential value of psychoeducation in schizophrenia, see the Psychiatric News article “Psychosocial Treatments Found Effective for Early Psychosis.”

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APA Supports ECT Device Reclassification; File Your Comments Now

APA strongly supports the U.S. Food and Drug Administration’s proposed reclassification of electroconvulsive therapy (ECT) devices from the more restrictive Class III (high risk) to Class II (low risk), wrote APA leaders yesterday in a letter to FDA Commissioner Robert Califf, M.D.

“[R]esearch consistently shows substantial rates of response and remission of treatment-resistant major depressive episodes to ECT, particularly when compared to response of treatment-resistant depression to additional trials of pharmacotherapy. In addition, analyses show rates of remission and response in individuals with bipolar depressive episodes that are generally comparable to that observed with major depressive disorder,” wrote APA President Renée Binder, M.D., and CEO and Medical Director Saul Levin, M.D., M.P.A. “These data provide further support for the proposed reclassification of ECT devices to class II for major depressive episodes.”

The leaders went on to recommend that the Class II designation be given for catatonia, mania in bipolar disorder, schizophrenia, and schizoaffective disorder and include ECT treatment for children and adolescents meeting the criteria for treatment resistance and in need of a potentially lifesaving intervention for the conditions previously indicated and for major depressive episodes associated with major depressive disorder or bipolar disorder.

“From a safety standpoint, as the FDA notes, ECT-related risks for these conditions are comparable for major depressive episodes. Evidence from peer-reviewed scientific literature, which meets the FDA definition of valid scientific evidence, supports the benefits of ECT in these conditions,” Binder and Levin wrote.

APA members are encouraged to submit a formal comment on the Federal Register site that explains why this reclassification could greatly improve access to safe, effective treatment for individuals with serious and persistent psychiatric disorders. A template letter has been prepared that provides talking points. The FDA must receive comments by March 28. As of 11:59 p.m. yesterday, the FDA had received 922 comments, and many of the comments reflect opposition to the proposal.

In 2009, the FDA also opened a public docket to receive comments regarding a similar reclassification proposal that closed in January 2010. At the time, the agency received over 3,000 submissions, with the majority of respondents (approximately 80 percent) opposing reclassification of ECT devices, and did not proceed with the reclassification.

“[I]t is so important for psychiatrists to take the lead in expressing their views in regard to the role that ECT plays in clinical practice and in the treatment of major depressive disorder,” Levin and Binder wrote in a blog post about the proposal. “For appropriate patients, ECT has been a lifesaver. It has given them an opportunity for a normal, functional life.”

For more information in Psychiatric News about prior efforts to reclassify ECT devices, see “FDA Advisory Panel Favors ECT in High-Risk Category.”

Test May Offer Clues About Elderly Patients Likely to Benefit From Aripiprazole

Elderly patients with major depressive disorder (MDD) who score well on a test that measures the ability to shift attention between tasks may be more likely to respond to augmentation with aripiprazole after failing to respond to first-line therapy with venlafaxine, according to a study published yesterday in JAMA Psychiatry. The findings suggest standardized neuropsychological tests of this cognitive process could one day help to guide therapeutic decisions.

Over half of older adults with MDD do not adequately respond to first-line pharmacotherapy with selective serotonin reuptake inhibitors or selective serotonin-norepinephrine reuptake inhibitors. In September 2015, Charles Reynolds III, M.D., a professor of geriatric psychiatry at the University of Pittsburgh, and colleagues published findings that showed that adding aripiprazole to the treatment regimen of patients aged 60 and older whose major depression had failed to remit after 12 weeks of venlafaxine monotherapy helped more patients achieve remission than those who did not take the combination of medications.

As a follow-up to this trial, the researchers examined the potential moderating effects of executive dysfunction, comorbid anxiety, and medical burden in remission of treatment-resistant late-life depression after 12 weeks of aripiprazole augmentation. (All of these factors have been implicated in contributing to poor antidepressant responses in late-life depression, but they have not previously been examined in second-line therapies.)

Prior to starting the 12 weeks of venlafaxine extended-release treatment, study participants were given a series of neuropsychological tests, including the Color-Word Interference task, which measures response inhibition, and the Trail Making Test tasks, which measures set-shifting (the ability to shift attention from one task to another). Researchers also used the Brief Symptom Inventory and Cumulative Illness Rating Scale for Geriatrics to assess comorbid anxiety and medical burden, respectively.

Of the 181 trial participants whose major depression had failed to remit with venlafaxine hydrochloride monotherapy (150 mg/day to 300 mg/day for 12 weeks), 91 received aripiprazole (target dose 10 mg/day), and 90 received placebo. Remission occurred in 40 (43%) who received aripiprazole and 26 (29%) who received placebo. Set-shifting performance was found to moderate the effectiveness of aripiprazole augmentation; among participants with a Trail Making Test scaled score of 7 or higher, the odds of remission were significantly higher with aripiprazole than with placebo (53% vs 28%). Among participants with a Trail Making Test scaled score of less than 7, aripiprazole and placebo were equally efficacious. Greater severity of anxiety at baseline predicted a lower remission rate but did not moderate aripiprazole efficacy; each standard deviation greater anxiety severity was associated with 50% reduced odds of remission in both aripiprazole and placebo arms. Neither medical morbidity nor response inhibition was related to remission.

“Our findings support set-shifting performance as a moderator of short-term remission (i.e., influencing the efficacy of aripiprazole) and distinguish anxiety as a general short-term prognostic variable (predictor),” the authors wrote. “Further examining a wider range of pretreatment factors, including other aspects of cognition, as well as the neurobiological basis of these observed effects, will continue to improve our understanding of how treatments work and for whom they do or do not work.”

In a related editorial, Warren Taylor, M.D., an associate professor of psychiatry at Vanderbilt University Medical Center, offered several reflections on the implications of the findings for clinical treatment and clinical trial methodology.

“Although this study’s findings require replication, the potential for using a common, easy-to-administer neuropsychological test to personalize antidepressant treatment decisions for older adults is appealing. However, even with this approach, remission rates continue to be lower than we would like,” Taylor wrote. “This study’s findings are thus a step forward, but it also highlights the need for more effective interventions, particularly for individuals with executive dysfunction or substantial comorbid anxiety.”

For related information, see the Psychiatric News article “Combining Aripiprazole, Venlafaxine Reduces Depressive Symptoms in Older Adults.”

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Alpha-7 Agonist Found to Improve Cognition in Non-Smoking Patients With Schizophrenia

A study published in AJP in Advance suggests ABT-126—a selective alpha-7 (α7) nicotinic receptor partial agonist—may help improve cognition in patients with schizophrenia, but the medication showed significant effects only in those who were nonsmokers.

Although current therapies for schizophrenia have been shown to significantly improve positive symptoms of the disorder, none of them noticeably improves cognition. Previous studies suggest that α7 neuronal nicotinic receptors play a key role in cognitive function, and trials of ABT-126 suggest the medication is well tolerated by patients with Alzheimer’s disease and schizophrenia (up to 150 mg once daily).

To assess the effectiveness and safety of ABT-126 in the treatment of cognitive impairment, researchers from Cairo University in Egypt and AbbVie Inc., manufacturer of ABT-126, randomly assigned 207 clinically stable patients with schizophrenia to receive 10 mg of ABT-126, 25 mg of ABT-126, or placebo once daily for 12 weeks. The primary efficacy measure was the change from baseline to study endpoint on the MATRICS Consensus Cognitive Battery (MCCB) composite score. Secondary measures included changes in specific domains scores on the MCCB such as verbal learning and working memory.

The researchers found that ABT-126 demonstrated a dose-dependent improvement on cognition that trended toward but did not achieve statistical significance in the 165 patients who completed the trial. Additional subset analyses revealed that nonsmokers taking ABT-126 showed a significant improvement in overall MCCB scores compared with placebo, whereas smokers taking ABT-126 did not. In addition, nonsmokers treated with 25 mg of ABT-126 showed significant improvements in domain scores for verbal learning, working memory, and attention/vigilance.

“No meaningful changes in the severity of schizophrenia symptoms, as measured by the PANSS and its positive and negative symptom subscales, and specifically negative symptoms, as measured by the Negative Symptom Assessment, were observed in the total sample or in subgroups defined by smoking status or baseline level of negative symptoms,” the researchers added. “These results suggest that the improvements in cognition during treatment with ABT-126 were independent of changes in schizophrenia symptoms and that ABT-126 did not worsen the underlying psychotic illness.”

The researchers hypothesized that chronic nicotine exposure from tobacco smoke may render nicotinic receptors ineffective, but noted more research is needed to evaluate the effectiveness of ABT-126 in smokers and nonsmokers.

For related news, see the Psychiatric News article “Twelve Drugs in Pipeline Hope to Address Psychosis-Related Cognitive Function.”

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Medicaid Coverage of Methadone Maintenance Linked to Use of Medication Assisted Treatment

Medicaid enrollees with opioid use disorders in states that cover methadone maintenance may be more likely to receive opioid agonist therapy (OAT) than those in states that do not cover this benefit, according to a report appearing in Psychiatric Services in Advance. The authors suggest the findings support Medicaid methadone maintenance coverage as critical for encouraging OAT among individuals with opioid use disorders.

Health services researchers from the Department of Health Policy and Management at Johns Hopkins University Bloomberg School of Public Health obtained information on states’ methadone maintenance coverage from a 2013 mail survey of Medicaid programs in all 50 states and the District of Columbia. The survey was conducted on behalf of the American Society of Addiction Medicine, which categorizes states into three mutually exclusive groups: states paying for methadone maintenance in the Medicaid fee-for-service benefit, states covering it only through Substance Abuse Prevention and Treatment (SAPT) block grants, and states with no public coverage of methadone maintenance. (States where methadone maintenance was covered through both Medicaid and SAPT were not separately identified.)

The researchers linked these state-level measures to the 2012 Treatment Episode Data Set, a database that annually includes information on 1.7 million public-sector substance abuse treatment admissions. They restricted the sample to Medicaid enrollees admitted to treatment for opioid use disorders (heroin or opioid analgesics), focusing on differences in use of OAT across three treatment settings: residential, intensive outpatient (three or more days per week, each with sessions of two or more hours), and non-intensive outpatient.

Overall, 7.0% of Medicaid enrollees in treatment for opioid use received OAT in states with no methadone coverage, whereas 46.6% received OAT in states with a Medicaid benefit that covers methadone maintenance, and 26.3% received OAT in states funding methadone only through a SAPT block grant. Non-intensive outpatient was the most common treatment setting.

In comments to Psychiatric News, John Renner, M.D. (pictured above), vice chair of the APA Council on Addiction Psychiatry, said the findings have important implications for addressing the nation’s opioid abuse epidemic. “The findings demonstrate that the most effective way to expand the availability of evidence-based medication assisted treatment (MAT) for individuals with opioid use disorder is to expand Medicaid coverage and to include MAT as a covered benefit,” Renner told Psychiatric News.

For related information, see the Psychiatric News article “California Psychiatrist Helps Develop Integrated Substance Abuse Care.”

Insurance Authorization Requirements Delay Care for Child, Adolescent Psychiatric Patients

A study in the American Journal of Emergency Medicine suggests child and adolescent psychiatric patients in need of immediate hospital admission often wait an hour before the admission authorizations required by insurance companies are approved. According to the authors, such delays put a significant burden on psychiatric clinicians and can create safety risks.

For this analysis, licensed social workers at Rhode Island’s Hasbro Children’s Hospital emergency room completed paperwork each time they contacted an insurance company on behalf of a child deemed in need of psychiatric admission.

Over a five-month period, 203 requests for psychiatric admission authorization of youth aged 4 to 19 took place. The most common reasons for admission included suicidal ideation or a suicide attempt, aggression, and homicidal ideation. The average time required to obtain insurance authorization was 59.8 minutes (overall times ranged from 3 minutes to 270 minutes). While there were variations in time required for authorization based on insurance type, all 203 requests for authorization were granted.

“Given that 100% of our attempts to obtain authorization were granted, the need to obtain prior authorizations appears to function more as an administrative hurdle rather than an effective triage to deny care, because if professionals know they or their colleagues are going to have to spend lengthy amounts of time on the phone with the insurance company, they may think twice prior to trying to admit a given patient,” the authors wrote.

“Insurance reviews and pre-authorization requests are just a part of what makes accessing needed psychiatric care difficult for children and adolescents… Adding prior authorization to an already difficult process, especially for psychiatric patients who are deemed to be of ‘imminent risk’ to themselves or others, seems both dangerous and predatory,” they concluded.

For related information, see the Psychiatric News article “Emergency Department Finds Successful Formula for Psychiatric Cases.”

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All-Cause Mortality Found to Be Higher in Women With Severe Postpartum Psychiatric Disorders

Women with first-onset episodes of severe postpartum psychiatric disorders had all-cause mortality rate ratios (MRRs) that were nearly four times higher than mothers with no previous psychiatric history, according to a report appearing today in AJP in Advance.

Importantly, the study found that the first year after diagnosis represented a time of very high relative suicide risk for the group of women with severe postpartum psychiatric disorders.

Danish researchers collected data on all women born in Denmark on Jan. 1, 1950, or later. The study cohort included 1,545,857 women who were followed from age 15 until death, emigration from Denmark, or until Dec. 31, 2011, whichever came first. (This time frame provided a maximum follow-up period of 42 years and a maximum age of 62 for the women in the cohort.)

The main exposure variable was defined as any first psychiatric inpatient or outpatient contact within the first 90 days postpartum. The main outcome measure was mortality rate ratios for deaths from natural or unnatural causes (such as death by suicide or accidents).

Of the 1,545,857 cohort members, 2,699 women had a first psychiatric contact recorded at an inpatient or outpatient treatment facility within three months after giving birth. Of these, 96 women died during the follow-up period.

Women with postpartum psychiatric disorders had a higher MRR (3.74) than women with children who had first inpatient or outpatient psychiatric contact outside the postpartum period (2.73) when compared with mothers with no psychiatric history. Unnatural cause of death represented 40.6% of fatalities among women with postpartum psychiatric disorders, and within the first year after diagnosis the suicide risk was drastically increased (MRR=289.42). In comparison, only 9.34% of mothers with no history of psychiatric disorders died from unnatural causes.

“The observed high relative risk of suicide in the postpartum period warrants special attention for this vulnerable group of women,” the authors stated. They proposed several recommendations based on the findings, emphasizing the need for clinicians to be alert to anxiety in women with postpartum mood symptoms, as “they are at a higher risk of self-harm because of the uncomfortable agitation they experience.”

The researchers concluded: “Screening programs of new mothers can increase awareness by providing important psychoeducation to mothers and by alerting health care providers of women who are experiencing suicidal thoughts.”

For more information, see the Psychiatric News article “Early Postpartum Depression Screenings Not Enough to Identify High-Risk Women.”

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Children Taking ADHD Medications May Have Decreased Bone Density

Youth who are taking medications prescribed for attention-deficit/hyperactivity disorder (ADHD) exhibit significantly diminished bone mineral density compared with those who are not taking the medications, researchers reported today at the 2016 annual meeting of the American Academy of Orthopaedic Surgeons in Orlando, Fla.

The researchers drew on data collected in the National Health and Nutrition Examination Survey between 2005 and 2010 from 5,315 children aged 8 to 17. Bone mineral density (BMD) scans revealed that children taking methylphenidate, dexmethylphenidate, dextroamphetamine, atomoxetine, or lisdexamfetamine had lower bone density in the femur, femoral neck, and lumbar spine regions.

“The findings suggest that there are real and non-trivial decreases in BMD for children and adolescents taking ADHD medications, as compared to similar children not taking any prescription medications,” said Jessica Rivera, M.D., an orthopaedic surgeon with the U.S. Army Institute of Surgical Research at Fort Sam Houston, Texas, and colleagues.

About 25% of the medicated children met criteria for osteopenia (a condition characterized by lower than normal bone density). A link between childhood osteopenia and osteoporosis in older adults has not been firmly established, but since most skeletal growth occurs before age 20, “prescribing physicians and parents should be aware of potential bone health risks associated with these medications,” said Rivera.

“The findings suggest an interesting association but the results don’t demonstrate causality,” commented child psychiatrist David Fassler, M.D., of Burlington, Vt. “A variety of potential intervening variables, such as diet and exercise, should be considered and explored before drawing conclusions regarding the implications of the current study.”

“If their data are replicated in prospective, longitudinal studies, the authors’ findings would certainly be a major cause for concern,” said Sylvia Karasu, M.D., a clinical professor of psychiatry at Weill Cornell Medicine in New York City. However, she noted medication use by self-report can be notoriously inaccurate, the researchers did not have data on dosage or duration of medication use, and changes in bone mass density were not measured over time.

For more in Psychiatric News about the link between psychiatric medications and bone health, as described by Karasu, see “Psychotropic Medication and Osteoporosis.”

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Study Suggests Factors Predictive of Violent Behavior in People With Mental Illness

Results from a meta-analysis in Psychiatric Services in Advance shows that three factors may be associated with an increased risk for adults with mental illnesses to commit community violence in the near future. They are alcohol use, exhibiting violent behaviors, and being a victim of violence within the past six months. The findings, the authors suggested, have the potential to help mental health professionals identify those patients who may be at risk to be violent, allowing intervention and possible prevention.

The analysis included information of more than 2,500 individuals from five previous studies with mental illnesses—including schizophrenia, bipolar disorder, major depressive disorder, and substance use disorder—who were surveyed at both baseline and six-month follow-up on their exposure to violence (being a perpetrator or victim), alcohol and drug use, psychiatric symptoms, and psychiatric hospitalization in the past six-months. Violent behaviors ranged from pushing and shoving to sexual assault and assault with a deadly weapon and were assessed by the MacArthur Community Violence Screening Instrument. Data were adjusted for age, sex, race, and primary diagnosis.

“This study provides empirical evidence for three proximal, clinically relevant indicators in the assessment and management of short-term violence risk among adults with mental illnesses,” the study authors wrote. “Although clinicians may never be able to answer the public calls for the absolute prediction—and prevention—of violence by adults with mental illnesses, attending to these indicators in clinical practice should assist in the identification of persons [who may be] at heightened risk of community-based violence.”

For related information, see the Psychiatric News article “What Is My Duty to Warn?"

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Study Documents Rise in Benzodiazepine Use, Overdose Deaths

Between 1996 and 2013, the rate of overdose deaths related to use of benzodiazepines rose from 0.58 per 1,000 adults to 3.07 per 1,000 adults, according to a report in the American Journal of Public Health.

While the study found that the overall rate of overdose deaths involving benzodiazepines plateaued in 2010, in some groups—adults aged 65 and older, blacks, and Hispanics—these rates continued to increase throughout the study period.

Marcus A. Bachhuber, M.D., M.S.H.P., assistant professor of medicine at Montefiore Medical Center/Albert Einstein College of Medicine, and colleagues examined data from the Medical Expenditure Panel Survey and multiple cause-of-death data from the Centers for Disease Control and Prevention.

Between 1996 and 2013, the number of adults filling a benzodiazepine prescription increased 67 percent, from 8.1 to 13.5 million. Among those filling benzodiazepine prescriptions, the median cumulative quantity filled over the year increased by 140%, from 86.8 mg to 208.0 mg lorazepam equivalents. Meanwhile, the rate of overdose fatalities involving benzodiazepines rose nearly fourfold in the 17-year period.

Bachhuber and colleagues suggested several possible explanations for factors driving overdose mortality: “Among people who filled benzodiazepine prescriptions, the median quantity filled over the year more than doubled between 1996 and 2013, suggesting either a higher daily dose or more days of treatment, which potentially increased the risk of fatal overdose,” they wrote. “Second, people at high risk for fatal overdose may be obtaining diverted benzodiazepines …Finally, increases in alcohol use or combining benzodiazepines with other medications (such as opioid analgesics) could increase the risk of fatal overdose and explain this rise.”

For more information, see the Psychiatric News article “Benzodiazepines: Experts Urge Balance.”

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